Apparatus and method for adjustment of ion separation resolution in FAIMS

ABSTRACT

An apparatus for controllably varying specificity of a FAIMS-based ion separation includes a FAIMS analyzer region defined between a first electrode surface and a second other electrode surface. The FAIMS analyzer region is in communication with an ionization source for providing a flow of ions including a known ion, and with an ion outlet for extracting ions including the known ion from the FAIMS analyzer region. The first and second electrode surfaces are for having an asymmetric waveform voltage applied thereacross for defining an average ion flow path for the known ion traversing therebetween. An actuator is provided for controllably moving the first electrode surface relative to the second electrode surface for controllably varying the length of the average ion flow path.

This application claims benefit from U.S. Provisional application60/630,193 filed Nov. 24, 2004, the entire contents of which areincorporated herein by reference.

FIELD OF THE INVENTION

The instant invention relates generally to High Field AsymmetricWaveform Ion Mobility Spectrometry (FAIMS), and more particularly to anapparatus and method for controllably varying specificity of aFAIMS-based ion separation.

BACKGROUND OF THE INVENTION

High sensitivity and amenability to miniaturization for field-portableapplications have helped to make ion mobility spectrometry (IMS) animportant technique for the detection of many compounds, includingnarcotics, explosives, and chemical warfare agents as described, forexample, by G. Eiceman and Z. Karpas in their book entitled “IonMobility Spectrometry” (CRC, Boca Raton, 1994). In IMS, gas-phase ionmobilities are determined using a drift tube with a constant electricfield. Ions are separated in the drift tube on the basis of differencesin their drift velocities. At low electric field strength, for example200 V/cm, the drift velocity of an ion is proportional to the appliedelectric field strength, and the mobility, K, which is determined fromexperimentation, is independent of the applied electric field.Additionally, in IMS the ions travel through a bath gas that is atsufficiently high pressure that the ions rapidly reach constant velocitywhen driven by the force of an electric field that is constant both intime and location. This is to be clearly distinguished from thosetechniques, most of which are related to mass spectrometry, in which thegas pressure is sufficiently low that, if under the influence of aconstant electric field, the ions continue to accelerate.

E. A. Mason and E. W. McDaniel in their book entitled “TransportProperties of Ions in Gases” (Wiley, New York, 1988) teach that at highelectric field strength, for instance fields stronger than approximately5,000 V/cm, the ion drift velocity is no longer directly proportional tothe applied electric field, and K is better represented by K_(H), anon-constant high field mobility term. The dependence of K_(H) on theapplied electric field has been the basis for the development of highfield asymmetric waveform ion mobility spectrometry (FAIMS). Ions areseparated in FAIMS on the basis of a difference in the mobility of anion at high field strength, K_(H), relative to the mobility of the ionat low field strength, K. In other words, the ions are separated due tothe compound dependent behavior of K_(H) as a function of the appliedelectric field strength.

In general, a device for separating ions according to the FAIMSprinciple has an analyzer region that is defined by a space betweenfirst and second spaced-apart electrodes. The first electrode ismaintained at a selected dc voltage, often at ground potential, whilethe second electrode has an asymmetric waveform V(t) applied to it. Theasymmetric waveform V(t) is composed of a repeating pattern including ahigh voltage component, V_(H), lasting for a short period of time t_(H)and a lower voltage component, V_(L), of opposite polarity, lasting alonger period of time t_(L). The waveform is synthesized such that theintegrated voltage-time product, and thus the field-time product,applied to the second electrode during each complete cycle of thewaveform is zero, for instance V_(H)t_(H)+V_(L)t_(L)=0; for example+2000 V for 10 μs followed by −1000 V for 20 μs. The peak voltage duringthe shorter, high voltage portion of the waveform is called the“dispersion voltage” or DV, which is identically referred to as theapplied asymmetric waveform voltage.

Generally, the ions that are to be separated are entrained in a streamof gas flowing through the FAIMS analyzer region, for example between apair of horizontally oriented, spaced-apart electrodes. Accordingly, thenet motion of an ion within the analyzer region is the sum of ahorizontal x-axis component due to the stream of gas and a transversey-axis component due to the applied electric field. During the highvoltage portion of the waveform, an ion moves with a y-axis velocitycomponent given by V_(H)=K_(H)E_(H), where E_(H) is the applied field,and K_(H) is the high field ion mobility under operating electric field,pressure and temperature conditions. The distance traveled by the ionduring the high voltage portion of the waveform is given byd_(H)=v_(H)t_(H)=K_(H)E_(H)t_(H), where t_(H) is the time period of theapplied high voltage. During the longer duration, opposite polarity, lowvoltage portion of the asymmetric waveform, the y-axis velocitycomponent of the ion is v_(L)=KE_(L), where K is the low field ionmobility under operating pressure and temperature conditions. Thedistance traveled is d_(L)=v_(L)t_(L)=KE_(L)t_(L). Since the asymmetricwaveform ensures that (V_(H) t_(H))+(V_(L) t_(L))=0, the field-timeproducts E_(H)t_(H) and E_(L)t_(L) are equal in magnitude. Thus, ifK_(H) and K are identical, d_(H) and d_(L) are equal, and the ion isreturned to its original position along the y-axis during the negativecycle of the waveform. If at E_(H) the mobility K_(H)>K, the ionexperiences a net displacement from its original position relative tothe y-axis. For example, if a positive ion travels farther during thepositive portion of the waveform, for instance d_(H)>d_(L), then the ionmigrates away from the second electrode and eventually is neutralized atthe first electrode.

In order to reverse the transverse drift of the positive ion in theabove example, a constant negative dc voltage is applied to the secondelectrode. The difference between the dc voltage that is applied to thefirst electrode and the dc voltage that is applied to the secondelectrode is called the “compensation voltage” (CV). The CV prevents theion from migrating toward either the second or the first electrode. Ifions derived from two compounds respond differently to the applied highstrength electric fields, the ratio of K_(H) to K may be different foreach compound. Consequently, the magnitude of the CV that is necessaryto prevent the drift of the ion toward either electrode is alsodifferent for each compound. Thus, when a mixture including severalspecies of ions, each with a unique K_(H)/K ratio, is being analyzed byFAIMS, only one species of ion is selectively transmitted to a detectorfor a given combination of CV and DV. In one type of FAIMS experiment,the applied CV is scanned with time, for instance the CV is slowlyramped or optionally the CV is stepped from one voltage to a nextvoltage, and a resulting intensity of transmitted ions is measured. Inthis way a CV spectrum showing the total ion current as a function ofCV, is obtained.

In an analytical instrument that includes (1) a condensed phaseseparation including for example one of liquid chromatography (LC) orcapillary electrophoresis, (2) an atmospheric pressure ionization sourceincluding for example electrospray ionization (ESI) or atmosphericpressure photoionization (APPI), (3) an atmospheric pressure gas phaseion separator including for example high-field asymmetric waveform ionmobility spectrometer (FAIMS) and (4) a detection system including forexample mass spectrometry (MS), it is advantageous to support switchingto convert the function of the intermediate gas phase separation device(FAIMS for example) from a mode of separation to a mode in which theions are not separated. This non-separating mode is called “total iontransmission mode” (TITM). The TITM is beneficial for reviewing themixture of ions that are arriving at the intermediate separation device,in order to assess whether any ions are being overlooked by applicationof the intermediate separation stage. The TITM mode in FAIMS isanalogous to the rf-only mode of a quadrupole mass spectrometer, inwhich mode of operation a wide range of ions is transmittedsimultaneously through the quadrupole. This rf-only mode supports tandemarrangement of several quadrupole devices, with one or more of thequadrupole devices operated optionally in non-separation mode so thatthe separation of ions only occurs in one of the series of tandemquadrupole devices.

SUMMARY OF THE INVENTION

It is an object of at least some embodiments of the instant invention toprovide a FAIMS device that is selectively operable in a firstseparation mode and in a second separation mode, the second separationmode having an ion separation resolution that differs from the firstseparation mode.

It is a further object of at least some of the embodiments of theinstant invention to provide a FAIMS device that is selectively operablein a conventional FAIMS separating mode and in a total ion transmissionmode (TITM).

According to an aspect of the instant invention, there is provided anapparatus for controllably varying specificity of a FAIMS-based ionseparation, comprising: a first electrode comprising a first electrodesurface; a second electrode comprising a second electrode surface, thesecond electrode spaced-apart from the first electrode along a firstdirection such that the second electrode surface faces the firstelectrode surface and overlaps therewith along a second direction thatis normal to the first direction so as to define a FAIMS analyzer regiontherebetween, the FAIMS analyzer region having an ion inlet end and anion outlet end, the first electrode and the second electrode movable onerelative to the other along the second direction for varying a length ofthe FAIMS analyzer region between the ion inlet end and the ion outletend; and, an actuator for controllably relatively moving the firstelectrode along the second direction relative to the second electrode,for varying the length of the FAIMS analyzer region between the ioninlet end and the ion outlet end.

According to an aspect of the instant invention, there is provided anapparatus for controllably varying specificity of a FAIMS-based ionseparation, comprising: a first generally cylindrical inner electrodehaving a first length; a second generally cylindrical inner electrodehaving a second length, the second generally cylindrical inner electrodeaxially aligned with and longitudinally spaced-apart from the firstgenerally cylindrical inner electrode so as to define a circumferentialgap between facing ends thereof, the circumferential gap defining an ioninlet; an outer generally cylindrical electrode having a third lengthand disposed in a concentric overlapping arrangement with the firstgenerally cylindrical inner electrode and with the second generallycylindrical inner electrode, the outer generally cylindrical electrodedefining an ion outlet within a portion thereof, a space between thesecond generally cylindrical inner electrode and the outer generallycylindrical electrode defining a FAIMS analyzer region, an average ionflow path being defined through said FAIMS analyzer region between theion inlet and the ion outlet; and, an actuator for relativelytranslating the outer generally cylindrical electrode relative to boththe first generally cylindrical inner electrode and the second generallycylindrical inner electrode, so as to vary a length of the average ionflow path between the ion inlet and the ion outlet.

According to an aspect of the instant invention, there is provided amethod for controllably varying specificity of a FAIMS-based ionseparation, comprising: providing a FAIMS analyzer region having an ioninlet for introducing a flow of ions thereto and having an ion outletfor extracting a subset of the flow of ions that is selectivelytransmitted along an average ion flow path between the ion inlet and theion outlet; introducing a first flow of ions into the FAIMS analyzerregion via the ion inlet; selectively transmitting a subset of the firstflow of ions along the average ion flow path through the FAIMS analyzerregion; relatively translating the ion inlet relative to the ion outletso as to provide an average ion flow path of a different length throughthe FAIMS analyzer region; and, transmitting ions of a second flow ofions along the average ion flow path of a different length.

According to an aspect of the instant invention, there is provided anapparatus for controllably varying specificity of a FAIMS-based ionseparation, comprising: a FAIMS analyzer region defined between a firstelectrode surface and a second other electrode surface, the FAIMSanalyzer region in communication with an ionization source for providinga flow of ions including a known ion, and with an ion outlet forextracting ions including the known ion from the FAIMS analyzer region,the first and second electrode surfaces for having an asymmetricwaveform voltage applied thereacross for defining an average ion flowpath for the known ion traversing therebetween; and, an actuator forcontrollably moving the first electrode surface relative to the secondelectrode surface for controllably varying the length of the average ionflow path.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the invention will now be described inconjunction with the following drawings, in which similar referencenumerals designate similar items:

FIG. 1 is a simplified block diagram showing a prior art tandemarrangement including an ion source, a FAIMS, and a mass spectrometer;

FIG. 2 is a longitudinal cross-sectional view of an electrospray ionsource disposed in fluid communication with an ion inlet of a FAIMS;

FIG. 3 is a longitudinal cross-sectional view of a parallel-plategeometry FAIMS, with a displacement of A between the openings in the topand middle plates and between the openings in the middle and lowerplates;

FIG. 4 is a longitudinal cross-sectional view of the FAIMS of FIG. 3with a displacement of B between the openings in the top and middleplates and between the openings in the middle and lower plates;

FIG. 5 is a longitudinal cross-sectional view of the FAIMS of FIG. 3with the openings in the top, middle and lower plates verticallyaligned;

FIG. 6 is a longitudinal cross-sectional view of a parallel-plategeometry FAIMS including a temperature controller for controlling thetemperature of the three plates;

FIG. 7 is a longitudinal cross-sectional view of the FAIMS of FIG. 6with the openings in the top, middle and lower plates verticallyaligned;

FIG. 8 a is a perspective view of one of the plates of the FAIMS of FIG.6, showing the heat-exchange fluid circulation system in greater detail;

FIG. 8 b is a plan view of the plate of FIG. 8 a;

FIG. 9 a is a perspective view of an optional flat plate design, inwhich the plate is absent sharp edges adjacent the inter-analyzeropening;

FIG. 9 b is an enlarged partial side cross-sectional view of the flatplate of FIG. 9 a, showing the shape of the inter-electrode opening ingreater detail;

FIG. 10 a is a side view of a cylindrical geometry FAIMS including along cylinder surrounding two shorter axially aligned cylinders, andhaving a source of ions proximate to a gap between the two shorteraligned cylinders;

FIG. 10 b is a simplified end view of the FAIMS of FIG. 10 a;

FIG. 11 is a side view of the FAIMS of FIG. 10 a with the two shorteraxially aligned cylinders translated longitudinally so that the gapbetween these cylinders is approximately adjacent to the ion outlet;

FIG. 12 is a side view of the FAIMS of FIG. 10 a with the ion outletproximate to the gap between the two shorter aligned cylinders;

FIG. 13 a is a cross sectional end view of a FAIMS in the form of threeelectrodes with curved adjacent surfaces, with approximate alignment ofthe ion inlet, the inter-analyzer opening and the ion outlet;

FIG. 13 b is a cross sectional end perspective view of the FAIMS of FIG.13 a with approximate alignment of the ion inlet, the inter-analyzeropening and the ion outlet;

FIG. 14 a is a cross sectional end perspective view of the FAIMS of FIG.13 a with a displacement of distance A between the ion inlet and theinter-analyzer opening and between the inter-analyzer opening and theion outlet;

FIG. 14 b is a cross sectional end perspective view of the FAIMS of FIG.13 a with a displacement of distance A between the ion inlet and theinter-analyzer opening and between the inter-analyzer opening and theion outlet, and showing ions flowing along an average ion flow pathbetween the ion inlet and the ion outlet

FIG. 15 a is a longitudinal cross-sectional view of a parallel-plategeometry FAIMS, with a displacement A between an ion inlet and atransition point and between the transition point and an ion outlet;

FIG. 15 b is a longitudinal cross-sectional view of the parallel-plategeometry FAIMS of FIG. 15 a, with a displacement B between the ion inletand the transition point and between the transition point and the ionoutlet;

FIG. 15 c is a longitudinal cross-sectional view of the parallel-plategeometry FAIMS of FIG. 15 a, in a total ion transmission operating mode;

FIG. 16 is a perspective view of the middle plate of the FAIMS system ofFIG. 15 a disposed in a spaced apart relationship relative to the curvedelectrode of the FAIMS system of FIG. 15 a, and showing an average ionflow path; and,

FIG. 17 is a simplified flow diagram of a method for controllablyvarying specificity of a FAIMS-based ion separation according to anembodiment of the instant invention.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The following description is presented to enable a person skilled in theart to make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe disclosed embodiments will be readily apparent to those skilled inthe art, and the general principles defined herein may be applied toother embodiments and applications without departing from the spirit andthe scope of the invention. Thus, the present invention is not intendedto be limited to the embodiments disclosed, but is to be accorded thewidest scope consistent with the principles and features disclosedherein. Throughout the detailed description and in the claims thatfollow, the following terms shall be accorded the definitions asfollows. An average ion flow path is defined as the net trajectory of anion as a result of a carrier gas flow through the analyzer region,although the individual ion also experiences an oscillatory motionbetween the electrodes as a result of the applied asymmetric waveformvoltage.

Throughout much of the following discussion it is assumed that the FAIMSelectrodes are operating at atmospheric pressure, but the discussion isequally applicable at pressures below ambient atmospheric pressure andat pressures exceeding ambient atmospheric pressure. Furthermore,because ion separation and ion transmission in FAIMS is susceptible tochanges in temperature it is desirable to operate FAIMS at a selectedtemperature setting. For example, a rise in temperature leads to adecrease in the number density of the gas (N, molecules per cc) andtherefore the operating electric field (E/N) increases with risingtemperature. Similarly an increase in gas pressure increases N andtherefore decreases the effective E/N conditions. In order thatexperiments give consistent results when repeated, it is assumed thatthe temperatures and pressures are maintained at selected conditions,within selected tolerance limits.

It is also assumed that the physical conditions in the analyzer regionof FAIMS do not significantly change the CV of the transmission of theion of interest while it is passing through the analyzer region to adegree that prevents its transmission. For example, if conditions indifferent areas of the analyzer region differ substantially, those ionsthat are initially being successfully transmitted near the ion inletregion likely are lost to the electrode walls at a later time duringtheir passage through the FAIMS analyzer region. This occurs, forinstance, when conditions near the ion inlet are in a balanced state fora selected ion type, and the selected ion type is being transmitted nearthe ion inlet, but at a location elsewhere in the analyzer region theconditions are sufficiently different that the same selected ion type ismigrating to the electrode walls and is being lost. Temperature,pressure, composition of the carrier gas and spacing between theelectrodes, are a few non-limiting examples of the physical conditions,assuming constant applied voltages, that affect the CV of transmissionof an ion. For example, a substantial difference in the electrodespacing near the ion inlet and near the ion outlet results in the fieldE/N near the inlet and near the outlet being different from each other.In some instances, moderate changes are beneficial for improving theresolution, or specificity, of ion separation, but larger changes thatthe ion experiences for longer times may result in complete loss oftransmission of the ion. The term specificity is intended to describethe number of different ion types actually transmitted through a FAIMSdevice relative to the number of different ion types that are introducedvia an ion inlet of the FAIMS. High specificity indicates that few oronly one type of ion is actually being transmitted through the FAIMS,whereas low specificity indicates that many or all types of ion areactually being transmitted through the FAIMS. Of course, iontransmission efficiency may vary significantly with ion type, or may berelatively constant for different ion types. Thus, a total iontransmission mode (TITM) is by definition a low specificity mode ofoperation in which at least some fraction of many or all types of ionsthat are introduced via an ion inlet are transmitted through the FAIMSdevice to an ion outlet.

Referring now to FIG. 1, shown is a simplified block diagram of a priorart tandem arrangement including a condensed phase separation system102, an ionization source 104, an ion desolvation region 106, a FAIMS108, and a mass spectrometer 110. A power supply 112 applies voltagesincluding an asymmetric waveform voltage and a compensation voltage tonot illustrated electrodes of the FAIMS 108 via electrical connection114. In FIG. 1 the ionization source 104 is shown, by way ofnon-limiting example, in the form of an electrospray ionization source.However, many other suitable ion sources are known, includingphotoionization sources, APCI sources, atmospheric pressure MALDI,radioactivity based sources, corona discharge sources, and otherrf-based discharge sources, to name just a few non-limiting examples.The components 104, and 106 optionally are at elevated temperature toassist in desolvation of the ions, whereas 102, 108, and 110 areoptionally at room temperature.

Referring still to FIG. 1, sample is provided from the condensed phaseseparation system 102 to ionization source 104. Ions produced from thesample are introduced into FAIMS 108 via desolvation region 106, and areseparated according to the FAIMS principle. Ions that are transmittedthrough FAIMS 108 then travel to mass spectrometer 110 to be analyzedfurther or detected.

Referring now to FIG. 2, shown is a longitudinal cross-sectional view ofan ESI-FAIMS-MS tandem system, shown generally at 200. An electrosprayionization needle 202 is disposed in fluid communication with an ioninlet 204 of a FAIMS 206. The inner electrode 208 and the outerelectrode 210 are supported in a spaced-apart arrangement by aninsulating material 212 with high dielectric strength to preventelectrical discharge. Some non-limiting examples of suitable materialsfor use as the insulating material 212 include Teflon™ and PEEK. Apassageway 214 for introducing a curtain gas is shown by dashed lines inFIG. 2, but often is omitted in later figures for simplicity ofinterpretation of the figures.

In FIG. 2, the ions are formed near the tip of electrospray needle 202and drift towards a curtain plate 216. The curtain gas, introduced belowthe curtain plate 216 via the passageway 214, divides into two portions,one of which flows through an aperture 218 in the curtain plate 216, soas to prevent neutrals and droplets from entering the curtain plateaperture 218. Ions are driven against this flow of gas by a voltagegradient that is established between the needle 202 and the curtainplate 216. A field generated by a voltage difference applied between thecurtain plate 216 and the FAIMS outer electrode 210 pushes ions thatpass through the aperture 218 in the curtain plate 216 towards the ioninlet 204 of FAIMS 206. The second portion of the curtain gas flows intothe ion inlet 204 and carries the ions along the length of the FAIMSelectrodes to an ion outlet 220, and into a not illustrated massspectrometer or other post-FAIMS analyzer/detector.

A high voltage asymmetric waveform is applied by electrical controller222 to the inner electrode 208 of FAIMS 206, to produce an electricfield that causes ions within an annular space between the innerelectrode 208 and the outer electrode 210, which annular space isreferred to as the analyzer region 224, to oscillate between the innerelectrode 208 and the outer electrode 210. The waveform is generated insuch a way to cause the ions to move in a first direction in a strongfield for a short time, followed by motion in the other direction in aweaker field for a longer time. Absent any change in ion mobilitybetween the high field and low field portions of this applied asymmetricwaveform, after each cycle of the waveform the ion returns to itsoriginal position relative to the surface of the electrodes, withoutconsideration of diffusion or ion-ion repulsion. In practice however,the mobility of many ions is different in strong and weak electricfields and for these ions the ion's position after one cycle of thewaveform is not identical to its starting position relative to theelectrode surfaces. A second, direct current voltage, which is referredto as the compensation voltage (CV), is applied to eliminate orcompensate for this change of position. If the compensation voltage isof a magnitude that eliminates or compensates for the change of positionthat otherwise occurs absent the compensation voltage, the ion returnsto the same relative location after each cycle of the waveform. Thus theion does not migrate towards one or the other of the electrodes, and istransmitted through FAIMS 206. Other ions, for which the compensationvoltage is too high or too low to compensate for the net displacement ofthe ion relative to the electrodes during one cycle of the waveform,drift towards an electrode and are unable to pass through FAIMS 206.

Still referring to FIG. 2, the cylindrical electrode geometry alsopermits ion focusing of the ion for which the asymmetric waveformvoltage and compensation voltages are appropriate for transmissionthrough FAIMS. This ion focusing mechanism means that ions, for whichthe compensation voltage exactly balances the change in position notedabove, do not travel parallel to the walls of the electrodes as they aretransported by the gas along the analyzer region 224. Under conditionsof focusing, the ions that were originally near the electrode wallsmigrate to an optimum radial location between the electrodes. The ioncloud therefore tends to be located around this optimum radial location,thus ‘focusing’ the ions into a band within the space between theelectrodes. Of course this cloud occupies a finite amount of spacebecause the focusing is not strong and because diffusion, ion-ionelectrostatic repulsion and other mechanical and chemical activity,including turbulence of the gas, tends to cause the ion cloud to spreadout in space. At equilibrium the forces expanding the cloud are balancedby the focusing action of the electric fields in the analyzer region ofFAIMS. This focusing effect is a result of the gradient of electricfield E/N between the electrodes. In this example the gradient isgenerated because the electrodes are of cylindrical geometry, one of thepossible physical geometries of electrodes that gives rise tonon-constant E/N in space between the electrodes.

Two approaches are discussed for operating FAIMS 206 in total iontransmission mode. In a first approach the asymmetric waveform isdeactivated and the inner electrode 208 and the outer electrode 210 areheld at a same voltage. In a not illustrated second approach theasymmetric waveform is deactivated and the inner electrode 208 isretracted, or translated, so that the tip of the hemispherical end ofthe inner electrode 208 is no longer between the ion inlet 204 and theion outlet 220. The voltages applied to the inner electrode 208 and tothe outer electrode 210 are established empirically, to produceoptimized ion transmission. In both of these approaches the mixture ofions that enters through ion inlet 204 is not separated by the FAIMSmechanism, and some of the non-separated mixture of ions exits throughthe ion outlet 220. The extent to which the ions are transmitted isinfluenced also by other mechanisms for relative selectivity of iontransmission, for example the relative rates of loss of various types ofions via diffusion. It is also important to note that the ion focusingproperties of FAIMS are not operative absent the asymmetric waveform,since the variation in E/N in the radial direction is not sufficient forfocusing, so that the ions are lost by mechanisms that include diffusionand ion-ion electrostatic mutual repulsion. Unfortunately, whenoperating in this optional non-separating mode, the length of the ionpath between the ion inlet 204 and the ion outlet 220 is long, and theefficiency of transmission of the ions between the ion inlet 204 and theion outlet 220 is low.

FIG. 3 is a longitudinal cross-sectional view of a parallel plate FAIMS300 including three stacked plates 302, 304 and 306, disposed in aspaced-apart relationship. The plates 302, 304 and 306 are stacked alonga first direction, referred to as the stacking direction, such that afirst electrode surface along plate 302 faces one side of theintermediate electrode plate 304, and a second electrode surface alongplate 306 faces a side of the intermediate electrode plate 304 that isopposite the one side. Ions that are produced by ion source 308 driftalong the first direction toward a curtain plate 310. A flow of acurtain gas 312, introduced below the curtain plate 310, divides intotwo portions, one of which flows outwardly through an aperture 314 inthe curtain plate 310, so as to prevent neutrals and droplets fromentering the curtain plate aperture 314. Ions are driven against thisflow of gas by a voltage gradient that is established between the ionsource 308 and the curtain plate 310. A field generated by a voltagedifference between the curtain plate 310 and the FAIMS plate 302 pushesions that pass through the aperture 314 in the curtain plate 310 towardsthe ion inlet 316 of FAIMS 300. The second portion of the curtain gasflows into the ion inlet 316 and carries the ions along the length ofthe FAIMS electrodes through the analyzer region 318 a, along a seconddirection that is normal to the first direction. A second carrier gasflow 320 is optionally provided to assist in carrying the ions along theanalyzer region 318 a.

The ions travel along an average ion flow path, as is describedhereinbelow. In particular, the ions travel an approximate distancealong the average ion flow path indicated as “A” from the inlet 316 toan orifice, referred to as inter-analyzer aperture 322. The ions arecarried by the flow of gas through the inter-analyzer aperture 322 intoa second analyzer region 318 b, and travel a second approximate distance“A” along the average ion flow path to the ion outlet 324. Accordingly,the inter-analyzer aperture defines a transition point, for changing thedirection of ion flow along the average ion flow path. Since theasymmetric waveform and dc offset voltage is applied to the plate 304from power supply 326, and assuming that the distance between plate 302and 304 and between plate 304 and 306 are approximately equal, bothanalyzer regions 318 a and 318 b operate to separate ions in asubstantially equivalent way. Optionally, to improve ion separationresolution, slightly different conditions are imposed in these analyzerregions 318 a and 318 b, for instance by varying electrode spacing or byapplication of different dc voltages to plates 302 and 306.

FIG. 4 is a longitudinal cross-sectional view of the FAIMS of FIG. 3,with the inter-analyzer aperture 322 located at a distance “B” from theion inlet 316. This system is designed such that the position of theinter-analyzer aperture 322 is selectable relative to the ion inlet 316and the ion outlet 324. For instance, an actuator 328 is provided fortranslating the intermediate electrode plate 304 along the seconddirection, so as to translate the transition point as defined by theinter-analyzer aperture 322, and thereby controllably vary a length ofthe average ion flow path. The actuator 328 is optionally one ofmanually operable and automatically operable. For instance, the actuator328 optionally includes a thumb-screw, an adjustable wheel or knob, orsome other manually operable control mechanism for supporting manualadjustment of the inter-analyzer aperture 322 position. Alternatively,the actuator 328 optionally includes a motor that drives the electrode304 in one of a continuous and a stepped manner via a linkage member.

FIG. 4 illustrates that this arrangement of electrodes provides thebenefit of an adjustable ion transit time, allowing the separation ofions and the efficiency of ion transmission to be establishedempirically by adjusting the position of the inter-analyzer aperture 322relative to the ion inlet 316 and the ion outlet 324. If the gas flowrate is sufficiently high that the ion residence time is too short toachieve a desired degree of separation of one type of ion from anothertype of ion, the distance B between the ion inlet 316 and theinter-analyzer aperture 322 is increased, for instance to distance “A”as shown previously in FIG. 3. Optionally this distance is adjusted bymechanical horizontal translation of plate 304, however, thoseknowledgeable in the field will appreciate that this distance is readilyadjusted in many different ways.

In principle, the device as configured in either of FIG. 3 and FIG. 4optionally is operated in a non-separating TITM by removal of theasymmetric waveform and the dc compensation voltage. In this conditionthe device shown in FIG. 3 and FIG. 4 passes a mixtures of ions withoutactive FAIMS-based separation however the mixture of ions is required totravel some distance between the closely spaced electrodes/plates andion transmission efficiency from the ion source to the post-FAIMSdetector/analyzer is expected to be reduced.

It is an unforeseen benefit of the system shown in FIG. 3 and FIG. 4that the distances “A” or “B” are optionally reduced effectively tozero, as shown in FIG. 5. This also has the advantage of de-activatingthe FAIMS, and thereby providing a readily available mechanism for totalion transmission mode (TITM). Referring now to FIG. 5, by aligning theion inlet 316, the inter-analyzer aperture 322 and the ion outlet 324,the ion separation mechanism of FAIMS is minimized, so that the majorityof ions passing through ion inlet 316 exit through the ion outlet 324.The transmission of ions is significantly higher with the alignment ofthe ion inlet 316, the inter-analyzer aperture 322 and the ion outlet324, than if the inter-analyzer aperture 322 remained located atdistance “A” or “B” as shown in FIGS. 3 and 4 with the asymmetricwaveform and the dc compensation voltage removed. Furthermore, in FIG. 5the ion transmission optionally is further controlled by removal of theapplied asymmetric waveform and replacement of the dc voltages appliedto plates 302, 304 and 306 with dc voltages that are determinedempirically to maximize the efficiency of transport of ions from the ioninlet 316 to the ion outlet 324.

Still referring to FIG. 5, assuming the widths of the analyzer regions318 a and 318 b are each 2 mm, the distance from the ion inlet 316 tothe ion outlet 324 is now only 4 mm plus the thickness of the plate 304.The efficiency of transport of ions through this non-separating FAIMS issignificantly higher than that of the system in the state shown in FIG.3 or FIG. 4 operated in non-separating mode by removal of the waveformvoltages, since for example in the system of FIG. 3 the ions traveltwice the distance “A”. Additionally, when operating in a non-separatingmode the ions are difficult to transport unless the dc voltages appliedto the plates 302, 304 and 306 are substantially equal, since anyvoltage difference adds an electric field that tends to force the ionsto collide with one of the plates. Referring again to FIG. 5, the dcvoltages applied to the plates 302, 304 and 306 are helpful in pullingthe ions through the three co-aligned openings, namely ion inlet 316,inter-analyzer aperture 322 and ion outlet 324.

Although the system shown in FIGS. 3 through 5 include three separateelectrode plates 302, 304 and 306, optionally the plates 302 and 306 arereplaced by a single formed electrode having a generally “C-shaped”structure, such that a first electrode surface portion of the formedelectrode faces one side of the intermediate electrode plate 304, and asecond electrode surface portion of the same formed electrode faces aside of the intermediate electrode plate 304 that is opposite the oneside.

Of course, the parallel plate version of FAIMS that is shown in FIGS. 3through 5 is known to lack focusing properties, other than at the edgesof the plates, in the absence of temperature gradients or any otherconditions creating an electric field gradient between the electrodes.Fortunately, when temperature conditions between the parallel plateelectrodes are established to mimic the E/N gradient in cylindricalgeometry FAIMS, a beneficial focusing effect occurs. The transmission ofions at a fixed CV requires control of the temperature in the analyzerregion, such that the CV conditions for transmission of a selected iondo not change significantly as the ion travels along the space betweenthe electrodes. By controlling the temperature of the carrier gas and bycontrolling the temperature of each of the electrodes to create atemperature gradient in the gas between the electrodes, ion focusingconditions are established in the parallel plate version of FAIMS.

FIG. 6 illustrates a FAIMS system 600 similar to that shown in FIGS. 3through 5, however a temperature controller is provided to control therelative temperatures of each of the three plates 602, 604 and 606.Three flows 608, 610 and 612 of a heating/cooling fluid, referred tomore generally as a heat-exchange fluid, are delivered to channels inthe plates 602, 604 and 606 respectively. The heat-exchange fluid passesthrough channels in the plate and exits from the three plates as flows608 b, 610 b and 612 b from plates 602, 604 and 606 respectively.Preferably these three heat-exchange fluid flows are circulated andtemperature controlled independently. The heat-exchange fluid flows areused to adjust and stabilize the temperatures of the three plates, withthe benefit of producing temperature gradients between the electrodes.The temperature gradient produces a gradient of E/N between the platesduring application of the asymmetric waveform and dc offset voltagesbetween the electrodes. The gradient of E/N is beneficially controlledto maximize the ion transmission through the analyzer regions 614 a and614 b.

Referring still to FIG. 6, ions that are produced by ion source 616drift toward a curtain plate 618. A flow of a curtain gas 620,introduced below the curtain plate 618, divides into two portions, oneof which flows outwardly through an aperture 622 in the curtain plate618, so as to prevent neutrals and droplets from entering the curtainplate aperture 622. Ions are driven against this flow of gas by avoltage gradient that is established between the ion source 616 and thecurtain plate 618. A field generated by a voltage difference between thecurtain plate 618 and the FAIMS plate 602 pushes ions that pass throughthe aperture 622 in the curtain plate 618 towards the ion inlet 624 ofFAIMS 600. The second portion of the curtain gas flows into the ioninlet 624 and carries the ions along the length of the FAIMS electrodesthrough the analyzer region 614 a. A second carrier gas flow 626 isoptionally provided to assist in carrying the ions along the analyzerregion 614 a.

The ions travel along an average ion flow path, as is describedhereinbelow. In particular, the ions travel an approximate distancealong the average ion flow path indicated as “A” from the inlet 624 toan orifice in the intermediate electrode plate 604, which is referred toas inter-analyzer aperture 628. The ions are carried by the flow of gasthrough the inter-analyzer aperture 628 into a second analyzer region614 b, and travel a second approximate distance “A” along the averageion flow path to the ion outlet 630. Accordingly, the inter-analyzeraperture 628 defines a transition point, for changing the direction ofion flow along the average ion flow path. Since the asymmetric waveformand dc offset voltage is applied to the plate 604 from power supply 632,and assuming that the distance between plate 602 and 604 and betweenplate 604 and 606 are approximately equal, both analyzer regions 614 aand 614 b operate to separate ions in a substantially equivalent way.Optionally, to improve resolution, slightly different conditions areimposed in these analyzer regions 614 a and 614 b, for instance byelectrode spacing variation or by application of different dc voltagesto plates 602 and 606.

FIG. 7 illustrates the same system that is shown in FIG. 6, but with theinter-analyzer aperture 628 located in alignment with the ion inlet 624and the ion outlet 630. For instance, an actuator 634 is provided fortranslating the intermediate electrode plate 604 along a directionparallel to the plates 602 and 606, so as to translate the transitionpoint as defined by the inter-analyzer aperture 628, and therebycontrollably vary a length of the average ion flow path. The actuator634 is optionally one of manually operable and automatically operable.For instance, the actuator 634 optionally includes a thumb-screw, anadjustable wheel or knob, or some other manually operable controlmechanism for supporting manual adjustment of the inter-analyzeraperture 628 position. Alternatively, the actuator 634 optionallyincludes a motor that drives the intermediate electrode plate 604 in oneof a continuous and a stepped manner via a linkage member. Withalignment of the three openings the ions that are delivered to ion inlet624 pass without separation to the ion outlet 630, with the deviceacting in total ion transmission mode. In this mode of operation, it ispreferable that the asymmetric waveform be deactivated, and dcpotentials placed on all three plates 602, 604 and 606. The dcpotentials are selected to maximize the efficiency of transmitting ionsfrom ion inlet 624 to ion outlet 630.

FIGS. 8 a and 8 b illustrate one approach to passing a heat-exchangefluid through the plates 602, 604 or 606 of the system shown in FIG. 6and FIG. 7. In the specific example that is shown in FIGS. 8 a and 8 b,a flow of the heat-exchange fluid enters plate 604 through a fluid inlet802, and having passed along a channel 804 within the plate, the fluidexits from fluid exit port 806. Optionally the plate is heated byresistive elements or thermoelectric elements embedded into the plate.Optionally, similar structure is provided for controlling temperature ofplates 602 and 606.

Referring now to FIG. 9 a and FIG. 9 b, shown is a perspective view andan enlarged partial side cross-sectional view, respectively, of anoptional flat plate design, in which the plate 902 is absent sharp edgesadjacent the inter-analyzer aperture 908. In the specific example thatis shown in FIG. 9 a, a flow of a heat-exchange fluid enters plate 902through a fluid inlet 904, and having passed along a not illustratedchannel within the plate, the heat-exchange fluid exits from fluid exitport 906. The periphery of inter-analyzer aperture 908 is curved so asto smoothly join the upper and lower surfaces of plate 902. The absenceof sharp edges on plate 902 adjacent the inter-analyzer aperture 908beneficially guides ions and gas flow through the inter-analyzeraperture 908 and reduces the possibility of electrical arcing betweenthe plate 902 and adjacent electrode surfaces.

The embodiments of the present invention that have been discussed withreference to FIGS. 3 through 7 beneficially provide a very thin andrelatively flat FAIMS device, which is readily positioned between asource of ions and the inlet of a post-FAIMS analyzer, such as forinstance a mass spectrometer or further FAIMS devices. Advantageously,neither the ionization source nor the post-FAIMS analyzer ismechanically moved during the switching between separation mode and thenon-separating TITM of FAIMS.

Referring now to FIGS. 10 a and 10 b, shown is a side view and asimplified end view, respectively, of a cylindrical geometry FAIMS 1000including a long outer cylinder 1002 surrounding a first inner cylinder1004 and a second inner cylinder 1006 that is axially aligned with thefirst inner cylinder 1004. In FIG. 10 a, the long outer cylinder istransparent, so as to show more clearly the inner components includingthe first inner cylinder 1004 and the second inner cylinder 1006. Notillustrated electrically insulating material supports the first innercylinder 1004 and the second inner cylinder 1006 relative to the longouter cylinder 1002, so as to maintain spacing therebetween.

A flow of liquid sample is provided through a sample delivery tube 1008to the tip of an ESI source needle 1010. Ions are produced and pushedoutward radially because of the high voltage applied to the ESI sourceneedle 1010. Appropriate voltages applied to the shorter second innercylinder 1006 and the long outer cylinder 1002 drive the ions outwardlyin a radial direction away from the source needle 1010 and through a gap1012 between the shorter second inner cylinder 1006 and the longer firstinner cylinder 1004. In this example, the asymmetric waveform and dcoffset compensation voltages are applied to the first inner cylinder1004 through not-illustrated electrical connections.

Referring still to FIGS. 10 a and 10 b, the ions pass radially outwardthrough the gap 1012 and are entrained in a flow of carrier gas that issupplied by carrier gas conduit 1014 to the annular space between theconcentric second inner cylinder 1006 and the long outer cylinder 1002.The carrier gas flow transports the ions along the annular analyzerregion 1016 from the gap 1012 to the ion outlet 1018. By application ofappropriate asymmetric waveform voltage and dc voltages to the firstinner cylinder 1004 and the long outer cylinder 1002, the ions areseparated during transport along the analyzer region 1016. A flow ofsampler gas provided to the sampler gas conduit 1020 serves to carryneutral molecules and solvent through the space inside of the longerfirst inner cylinder 1004, after which the gas and the entrainedmolecules exit from the system through a sampler gas exit conduit 1022.An exit flow of carrier gas is optionally transported out of carrier gasexit conduit 1024. The gas flows, that is to say, the flow throughcarrier gas conduit 1014, sampler gas conduit 1020, sampler gas exitconduit 1022 and carrier gas exit conduit 1024, are adjusted to ensurethat a stream of carrier gas passes into the gap 1012 between the secondinner cylinder 1006 and the first inner cylinder 1004. The stream ofcarrier gas that passes into the gap 1012 is moving in a directionopposite to that of the ions passing outwardly through the same gap1012, and thus acts to help desolvate the ions and to prevent neutralsfrom the needle 1010 from contaminating the portion of the carrier gasflow that passes along the analyzer region 1016.

Referring still to FIG. 10 a, there are two approaches to providing anon-separated mixture of ions to a post-FAIMS device 1026, such as forinstance one of a mass spectrometer, a further FAIMS device, or an iondetector as some non-limiting examples. In a first approach theasymmetric waveform is deactivated and the first inner cylinder 1004 andthe outer cylinder 1002 held at a same voltage. In a second approach theasymmetric waveform is deactivated and the first inner cylinder 1004 isretracted away from the second inner cylinder 1006 so that the end ofthe first inner cylinder 1004 is no longer between the ion source 1010and the ion outlet 1018. In both of these approaches the mixture of ionsproduced by the ion source 1010 is not separated by the FAIMS mechanism,and some of the non-separated mixture of ions exits through the ionoutlet 1018. Of course, other mechanisms for relative selectivity of iontransmission may still exist, for example if the relative rates of lossof various types of ions via diffusion are different. When operating inthese optional non-separating modes, the pathway between the ion source1010 and the ion outlet 1018 is long and the efficiency of transmissionof the ions is not high.

Referring now to FIG. 11, shown is a side view of the FAIMS of FIG. 10 awith the first inner cylinder 1004 and the second inner cylinder 1006translated longitudinally so that the gap 1012 between these cylindersis approximately adjacent to the ion outlet 1018. FIG. 11 illustratesthe FAIMS system 1000 during non-separating, total ion transmission modewhereas FIG. 10 a with the application of the asymmetric waveform and adc compensation voltage illustrates the FAIMS system 1000 during thenormal separating operating mode of FAIMS. The conversion between thenon-separating and the normal operating mode is achieved via thetranslation of the first inner cylinder 1004, the second inner cylinder1006, and the ionization source 1010, and via control of theabove-mentioned applied voltages. To this end, a not illustratedactuator is provided. The not illustrated actuator is similar to theactuator 328 or 634 as described above. These components are moved sothat the gap 1012 becomes aligned with the ion outlet 1018 in the outercylinder 1002. Accordingly, the actuator is for moving synchronously thefirst inner cylinder 1004, the second inner cylinder 1006 and theionization source 1010. The sample delivery tube 1008 must haveprovision to remain connected during this translation, and similarly thesample gas delivery conduit 1020 and the sampler gas exit conduit 1022are flexibly connected to support such translational motion of the innercomponents of FAIMS system 1000.

In FIG. 11, a flow of liquid sample is provided through the sampledelivery tube 1008 to the tip of the ESI source needle 1010. Ions areproduced and pushed outward radially because of the high voltage appliedto the ESI source needle 1010. Appropriate voltages applied to theshorter second inner cylinder 1006 and the long outer cylinder 1002drive the ions outwardly in a radial direction away from the sourceneedle 1010 and through the gap 1012 between the shorter second innercylinder 1006 and the longer first inner cylinder 1004. In this example,the appropriate voltage is applied to the first inner cylinder 1004through not-illustrated electrical connections.

Referring still to FIG. 11, the ions pass radially outward through thegap 1012 and travel to the ion outlet 1018 along an average ion flowpath that is substantially perpendicular to the cylinder surfaces.Accordingly, the length of the average ion flow path is approximatelyequal to the size of the annular space between an outer surface of thefirst inner cylinder 1004 and an inner surface of the long outercylinder 1002. The average ion flow path does not include a componentalong a direction that is parallel to the cylinder surfaces, and as suchthe ions are not separated according to the FAIMS principle.

Referring now to FIG. 12, shown is a side view of the FAIMS of FIG. 10 awith the outer cylinder 1002 translated longitudinally so that the ionoutlet 1018 is approximately adjacent to the gap 1012 between the firstinner cylinder 1004 and the second inner cylinder 1006. FIG. 12illustrates the FAIMS system 1000 during non-separating, total iontransmission mode whereas FIG. 10 a with the application of anasymmetric waveform and a dc compensation voltage illustrates the FAIMSsystem 1000 during the normal separating operating mode of FAIMS. Theconversion between the non-separating and the normal operating mode isachieved via the translation of the long outer cylinder 1002, as well asthe post-FAIMS device 1026, such as for instance one of a massspectrometer, a further FAIMS device, or an ion detector as somenon-limiting examples. To this end, a not illustrated actuator isprovided. The not illustrated actuator is similar to the actuator 328 or634 as described above. These components are moved so that the ionoutlet 1018 becomes aligned with the gap 1012 between the first innercylinder 1004 and the second inner cylinder 1006. Accordingly, theactuator is for moving synchronously the long outer cylinder 1006, andthe post FAIMS device 1026. Of course, translation of heavier or bulkierpost FAIMS devices, such as for instance a mass spectrometer, limits theapplicability of this approach. Smaller and more compact post FAIMSdevices, such as for instance a lightweight ion detector or anotherFAIMS device, are better suited for this approach.

Referring still to FIG. 12, the ions pass radially outward through thegap 1012 and travel to the ion outlet 1018 along an average ion flowpath that is substantially perpendicular to the cylinder surfaces.Accordingly, the length of the average ion flow path is approximatelyequal to the size of the annular space between an outer surface of thefirst inner cylinder 1004 and an inner surface of the long outercylinder 1002. The average ion flow path does not include a componentalong a direction that is parallel to the cylinder surfaces, and as suchthe ions are not separated according to the FAIMS principle.

FIG. 11 and FIG. 12 show two ways of relatively moving the ion outlet1018 relative to the gap 1012. In FIG. 11, only the inner components aretranslated, which reduces complexity. In contrast, FIG. 12 requirestranslation of the post-FAIMS device and therefore is more complexdepending on the post-FAIMS device. For ease of use, minimization of thenumber of components that require movement is desired. Furthermore,movement of heavier components, such as for instance the post FAIMSdevice 1026, is to be avoided when possible.

FIGS. 13 a and 13 b illustrate a FAIMS system 1300, in which the FAIMSelectrodes are cylindrical in geometry, thereby providing the beneficialeffects of ion focusing when operating in the normal FAIMS ionseparating mode. In addition, a single electrode within FAIMS 1300 isreadily translatable between two positions, one position that provides aFAIMS separation and a second position in which FAIMS separation isabsent. It is beneficial that the ionization source, which is not shownin FIGS. 13 a and 13 b, is not mechanically moved. It is also beneficialthat most of the FAIMS device is not moved and that the post-FAIMSsystem, which also is not shown in FIGS. 13 a and 13 b, is not movedduring the change of FAIMS to non-FAIMS operating mode.

Referring now to FIG. 13 a, a stream 1302 of ions from a not-illustratedionization source pass through an ion inlet opening 1304 in a firstcurved electrode 1306. The curved electrode 1306 is spaced apart from afirst curved surface 1308 of an intermediate electrode 1310. The ionspass through an inter-analyzer aperture 1312 in the intermediateelectrode 1310. A third curved electrode 1314 is adjacent to a secondcurved surface 1316 of the intermediate electrode 1310. The stream ofions passes through an ion outlet opening 1318 through the thirdelectrode 1314, and the stream of transmitted ions 1404 is delivered toan optional further analyzer, for example one of a FAIMS, a drift tubeIMS, and a mass spectrometer as non-limiting examples.

FIG. 13 b is a cross-sectional end perspective view of the FAIMS 1300 ofFIG. 13 a, with approximate alignment of the ion inlet 1304, theinter-analyzer aperture 1312 and the ion outlet 1318. FIG. 13 b is takenby cutting through the FAIMS 1300 in a plane that passes through thealigned ion inlet 1304, the inter-analyzer opening 1312 and the ionoutlet 1318, and in practice the device extends longitudinally on bothsides of this plane. Not-shown insulating material supports theelectrodes in the spaced apart arrangement that is shown in FIG. 13 b,and provides gas-tight seals that prevent gas from escaping around theperipheral parts of the electrodes. The not-shown insulating materialensures that gas flows into FAIMS 1300 only through the ion inlet 1304and flows out of FAIMS 1300 only through the ion outlet 1318.

Still referring to FIGS. 13 a and 13 b, although there are curvedregions between the electrodes, the alignment of the ion inlet 1304, theinter-analyzer opening 1312 and the ion outlet 1318 results in ionscrossing the regions between the electrodes in a radial directionrelative to the curvatures of the electrodes. This differs from aconventional mode of operation of ion separation in FAIMS where the ionsare carried along the space between the electrodes in a directiongenerally parallel to the surfaces of the electrodes. FIGS. 13 a and 13b illustrate the FAIMS device 1300 operating in a non-separating, totalion transmission mode. The distance between the ion inlet 1304 and theion outlet 1318 is minimized.

FIGS. 14 a and 14 b illustrate the FAIMS 1300 of FIG. 13 a, but with theintermediate electrode 1310 translated along the longitudinal directionso that the position of the inter-analyzer opening 1312 is displaced adistance “A” from the line-of-sight pathway between the ion inlet 1304and the ion outlet 1318. FIG. 14 b also illustrates an average ion flowpath followed by a stream of ions 1402 and passing through ion inlet1304, along a path approximately parallel to the surfaces of theelectrodes to the inter-analyzer opening 1312, passing through theinter-analyzer opening 1312 and again following a path approximatelyparallel to the surfaces of the electrodes to the ion outlet 1318. Thestream of ions 1404 that has passed through the ion outlet 1318 is thenprovided to a further not-shown post-FAIMS device that is optionally oneof a mass spectrometer, an ion detector, a drift type ion mobilityspectrometer, or to another FAIMS, as some non-limiting examples.

Still referring to FIGS. 14 a and 14 b, it is beneficial that theintermediate electrode 1310 is translatable for modifying the length ofthe path that the ions take when passing from the ion inlet 1304 to theion outlet 1318. The displacement of the inter-analyzer opening 1312 inFIGS. 14 a and 14 b results in a pathway approximately twice thedisplacement “A”. In normal ion separation mode with the asymmetricwaveform and dc compensating offset voltages applied to the intermediateelectrode 1310, the FAIMS separation takes place as the ions are carriedalong this pathway from the ion inlet 1304 to the inter-analyzer opening1312, and from the inter-analyzer opening 1312 to the ion outlet 1318.The electric fields vary in strength in the radial direction from eachof the curved electrodes 1306 and 1314 towards the intermediateelectrode 1310. This variation in electric field strength, E/N, and theapplied asymmetric waveform establishes the ion focusing mechanism thatis beneficially used to minimize the loss of ions of interest, which aretransmitted through FAIMS 1300 at the appropriate DV and CV, to theelectrode surfaces.

Still referring to FIGS. 14 a and 14 b, the time required for transitthrough this device is beneficially controlled by the relative offsetdistance “A” that the ions travel to pass through the intermediateelectrode. A longer distance “A” improves ion separation, but alsoincreases the period of time required for ions to travel through theFAIMS device. Similarly, the effective separation may be reduced for abeneficial change in the time response of the device when the distance“A” in FIGS. 14 a and 14 b is minimized. FIGS. 13 a and 13 b illustratethe condition at the extreme of “A” being nearly zero such that theseparation is not effective and the device operates in total iontransmission mode, where specificity is low. In this non-separating modethat is illustrated in FIGS. 13 a and 13 b, the asymmetric waveformoptionally is turned off, and dc voltages are applied to the threeelectrodes of FAIMS 1300 to maximize ion transmission efficiency betweenthe ion inlet 1304 and the ion outlet 1318.

Referring now to FIG. 15 a, shown is a longitudinal cross-sectional viewof a parallel plate FAIMS 1500 including three stacked plates 1502, 1504and 1506, disposed in a spaced-apart relationship. The central electrode1504 includes a curved terminus 1508 that is continuous with a firstelectrode surface 1510 on one side of the electrode 1504 and with asecond electrode surface 1512 on a second side of the electrode 1504that is opposite the first side. Ions that are produced by ion source1514 drift toward a curtain plate 1516. A flow of a curtain gas 1518,introduced below the curtain plate 1516, divides into two portions, oneof which flows outwardly through an aperture 1520 in the curtain plate1516 so as to prevent neutrals and droplets from entering the curtainplate aperture 1520. Ions are driven against this flow of gas by avoltage gradient that is established between the ion source 1514 and thecurtain plate 1516. A field generated by a voltage difference betweenthe curtain plate 1516 and the FAIMS plate 1502 pushes ions that passthrough the aperture 1520 in the curtain plate 1516 towards the ioninlet 1522 of FAIMS 1500. The second portion of the curtain gas flowsinto the ion inlet 1522 and carries the ions along the length of theFAIMS electrodes through the analyzer region 1524 a. A second carriergas flow 1526 is optionally provided to assist in carrying the ionsalong the analyzer region 1524 a. The ions travel an approximatedistance indicated as “A” from the inlet 1522 to a transition point1528, defined near the end of the terminus 1508. The ions are carried bythe flow of gas past the transition point 1528 and around the curvedterminus 1508 into a second analyzer region 1524 b, and travel a seconddistance “A” to the ion outlet 1530. Since the asymmetric waveform anddc offset voltage is applied to the plate 1504 from power supply 1536,and assuming that the distance between plate 1502 and 1504 and thedistance between plate 1504 and 1506 are approximately equal, bothanalyzer regions 1524 a and 1524 b operate to separate ions in asubstantially equivalent way. Optionally, to improve ion separationresolution, slightly different conditions are imposed in these analyzerregions 1524 a and 1524 b, by varying electrode spacing, by applicationof different dc voltages to plates 1502 and 1506 or by the applicationof different temperatures to the plates 1502 and 1506.

Referring still to FIG. 15 a, a curved electrode 1532 is disposedbetween the plates 1502 and 1506. The curved electrode 1532 includes aconcave electrode surface 1534 facing the curved terminus 1508. Theconcave electrode surface 1534 maintains an approximately constantspacing to the plate 1504 between the analyzer region 1524 a and theanalyzer region 1524 b. Optionally, the curved electrode 1532 iselectrically isolated from the electrode plates 1502 and 1506. Forinstance, not illustrated electrically insulating material is disposedbetween the ends of the curved electrode 1532 and the plates 1502 and1506. Of course, the electrically insulating material forms a gas-tightseal to the plates 1502 and 1506 whilst supporting sliding motion of thecurved electrode 1532. In that case, a dc voltage applied by optionalpower supply 1534 is independent of applied dc voltages to plates 1502and 1506. By selection of appropriate applied dc voltages to each of theplates, optimized conditions for transmitting ions past the transitionpoint 1528 are provided. Alternatively, the curved electrode 1532 is inelectrical contact with plates 1502 and 1506.

Referring now to FIG. 15 b, shown is a longitudinal cross-sectional viewof the FAIMS 1500 of FIG. 15 a, with the central electrode 1504 andcurved electrode 1532 translated relative to plates 1502 and 1506, suchthat the position of the transition point 1528 is displaced a distance“B” from the ion inlet 1522 and the ion outlet 1530. In particular, thecentral plate 1504 and curved electrode 1532 are translated by equalamounts along a same direction, such that the spacing between the curvedterminus 1508 and the concave surface 1534 is unchanged from the spacingshown in FIG. 15 a. Ions traveling along an average ion flow pathbetween the ion inlet 1522 and the ion outlet 1530 traverse a distanceof approximately twice the distance “B” plus the thickness of plate1504. Accordingly, given substantially identical operating conditions,ions spend less time being separated when the system 1500 is in thestate shown in FIG. 15 b compared to the state shown in FIG. 15 a, inwhich ions traverse a greater distance of approximately twice thedistance “A” plus the thickness of plate 1504. Thus, ions having similarFAIMS separation properties may be separated when the system 1500 is inthe state shown in FIG. 15 a, but may not be separated when the system1500 is in the state shown in FIG. 15 b. As such, varying the distancebetween the transition point 1528 and ion inlet 1522 and ion outlet 1530supports controllably varying specificity of a FAIMS-based ionseparation.

Referring now to FIG. 15 c, shown is a longitudinal cross-sectional viewof the FAIMS 1500 of FIG. 15 a, with the plate 1504 and curved electrode1532 translated away from each other, such that the plate 1504 is nolonger disposed in the line-of-sight pathway between the ion inlet 1522and the ion outlet 1530. In the state of system 1500 shown in FIG. 15 c,ions pass along a shortest ion pathway between the ion inlet 1522 andthe ion outlet 1530. Optionally, the asymmetric waveform applied toplate 1504 is shut off. Further optionally, an electric field gradientis established between plate 1502 and plate 1506 for driving ions fromthe ion inlet 1522 to the ion outlet 1530.

Referring still to FIG. 15 c, a not illustrated actuator for translatingthe plate 1504 independently of the curved electrode 1532 is provided.Optionally, the actuator also supports synchronized translation of theplate 1504 and of the curved electrode 1532, so as to vary the distancebetween transition point 1528 and the ion inlet 1522 and the ion outlet1530, as shown in FIGS. 15 a and 15 b, whilst maintaining approximatelythe same spacing from the curved terminus 1508 to the concave surface1534.

Referring now to FIG. 16, shown is a perspective view of the plate 1504disposed in a spaced apart relationship relative to the curved electrode1532. An average ion flow path 1600 is shown between the ion inlet 1522and the ion outlet 1530, and passing through the transition point 1528.

Optionally, a form of side-to-side FAIMS is obtained by modification ofthe device shown at FIGS. 15 a–15 c. For instance, the plate 1504 ismodified such that a second curved terminus is provided at an end of theplate 1504 opposite the curved terminus 1508. A second concave surfaceis disposed adjacent the second curved terminus, and the plate 1504arranged approximately symmetrically with respect to a line passingthrough the ion inlet 1522 and the ion outlet 1530. In this notillustrated alternative embodiment, a second average ion flow path isdefined between the ion inlet 1522 and the ion outlet 1530 that passesthrough a second transition point adjacent to the second curvedterminus. Optionally, during use the modified plate is translated alongone direction or the other, parallel to the plates 1502 and 1506. Inthis way, one of the average ion flow paths is lengthened, whilst thesecond average ion flow path is shortened. Alternatively, the modifiedplate is expandable, such that each of the two average ion flow paths isindependently variable. Of course, a system including an expandableelectrode plate is complicated, and provisions must be made to supportthe electrode plate and to ensure proper gas flow directionality.

Referring now to FIG. 17, shown is a simplified flow diagram of a methodfor controllably varying specificity of a FAIMS-based ion separationaccording to an embodiment of the instant invention. At step 1700 aFAIMS analyzer region is provided, the FAIMS analyzer region having anion inlet for introducing a flow of ions thereto and having an ionoutlet for extracting a subset of the flow of ions that is selectivelytransmitted along an average ion flow path between the ion inlet and theion outlet. At step 1702 a first flow of ions is introduced into theFAIMS analyzer region via the ion inlet. At step 1704 a subset of thefirst flow of ions is selectively transmitted along the average ion flowpath through the FAIMS analyzer region. At step 1706 the ion inlet isrelatively translated relative to the ion outlet so as to provide anaverage ion flow path of a different length through the FAIMS analyzerregion. At step 1708 ions of a second flow of ions are transmitted alongthe average ion flow path of a different length.

In one particular use, which is given by way of a non-limiting example,an ion composition of the first flow of ions is substantially the sameas an ion composition of the second flow of ions. For instance, thefirst and second flows of ions are produced at a same ionization sourcefrom a same sample material. Then, when having translated the ion inletrelative to the ion outlet to operate in the non-FAIMS separating TITMmode the ions of the second flow of ions that are transmitted along thesecond average ion flow path length has an ion composition substantiallythe same as the ion composition of the second flow of ions. In thiscase, the average ion flow path is equal to a straight-line distance orshortest path between the ion inlet and the ion outlet. Under thiscondition, the length of the FAIMS analyzer region is considered to beapproximately zero. Optionally, appropriate conditions such as forexample an electric field gradient between the ion inlet and the ionoutlet or an appropriate gas flow are provided for directing the ions ofthe second flow between the ion inlet and the ion outlet.

Numerous other embodiments may be envisaged without departing from thespirit and scope of the invention.

1. An apparatus for controllably varying specificity of a FAIMS-basedion separation, comprising: a first electrode comprising a firstelectrode surface; a second electrode comprising a second electrodesurface, the second electrode spaced-apart from the first electrodealong a first direction such that the second electrode surface faces thefirst electrode surface and overlaps therewith along a second directionthat is normal to the first direction so as to define a FAIMS analyzerregion therebetween, the FAIMS analyzer region having an ion inlet endand an ion outlet end, the first electrode and the second electrodemovable one relative to the other along the second direction for varyinga length of the FAIMS analyzer region between the ion inlet end and theion outlet end; and, an actuator for controllably relatively moving thefirst electrode along the second direction relative to the secondelectrode, for varying the length of the FAIMS analyzer region betweenthe ion inlet end and the ion outlet end.
 2. An apparatus according toclaim 1, wherein the actuator is for supporting controllable movement ofthe first electrode relative to the second electrode to a position inwhich the length of the FAIMS analyzer region is approximately zero. 3.An apparatus according to claim 1, wherein the actuator comprises amotor coupled to one of the first electrode and the second electrode viaa linkage member.
 4. An apparatus according to claim 1, wherein theactuator comprises a manually operable mechanism coupled to one of thefirst electrode and the second electrode.
 5. An apparatus according toclaim 1, wherein the first electrode and the second electrode compriseinner and outer generally cylindrical electrodes, respectively, disposedin a concentric arrangement relative to a longitudinal axis definedalong the second direction.
 6. An apparatus according to claim 5,comprising a second inner electrode longitudinally spaced apart from thefirst electrode and coaxial therewith, a gap between the first electrodeand the second inner electrode defining an ion inlet adjacent the ioninlet end, and further comprising an ion outlet defined within a portionof the second electrode and adjacent the ion outlet end.
 7. An apparatusaccording to claim 6, comprising an ionization source in fluidcommunication with the ion inlet end via the ion inlet.
 8. An apparatusaccording to claim 7, wherein the actuator is for translating the firstelectrode relative to the second electrode.
 9. An apparatus according toclaim 8, wherein the actuator is for translating the second innerelectrode synchronously with the first electrode, such that the gapbetween the first electrode and the second inner electrode isapproximately constant during translation.
 10. An apparatus according toclaim 7, wherein the actuator is for translating the second electroderelative to the first electrode.
 11. An apparatus for controllablyvarying specificity of a FAIMS-based ion separation, comprising: a firstgenerally cylindrical inner electrode having a first length; a secondgenerally cylindrical inner electrode having a second length, the secondgenerally cylindrical inner electrode axially aligned with andlongitudinally spaced-apart from the first generally cylindrical innerelectrode so as to define a circumferential gap between facing endsthereof, the circumferential gap defining an ion inlet; an outergenerally cylindrical electrode having a third length and disposed in aconcentric overlapping arrangement with the first generally cylindricalinner electrode and with the second generally cylindrical innerelectrode, the outer generally cylindrical electrode defining an ionoutlet within a portion thereof, a space between the second generallycylindrical inner electrode and the outer generally cylindricalelectrode defining a FAIMS analyzer region, an average ion flow pathbeing defined through said FAIMS analyzer region between the ion inletand the ion outlet; and, an actuator for relatively translating theouter generally cylindrical electrode relative to both the firstgenerally cylindrical inner electrode and the second generallycylindrical inner electrode, so as to vary a length of the average ionflow path between the ion inlet and the ion outlet.
 12. An apparatusaccording to claim 11, comprising an ionization source in fluidcommunication with the FAIMS analyzer region via the ion inlet.
 13. Anapparatus according to claim 12, wherein the ionization source is atleast partially contained within the first generally cylindrical innerelectrode.
 14. An apparatus according to claim 11, comprising anelectrical controller operatively coupled to the second generallycylindrical inner electrode for establishing an electric field betweenthe second generally cylindrical inner electrode and the outer generallycylindrical electrode by application of an asymmetric waveform voltageand a direct current compensation voltage.
 15. An apparatus according toclaim 11, comprising a temperature controller for controllablyestablishing a temperature gradient within a gas flow between the secondgenerally cylindrical inner electrode and the outer generallycylindrical electrode.
 16. An apparatus according to claim 11,comprising a temperature controller for controllably adjusting atemperature of at least one of the second generally cylindrical innerelectrode and the outer generally cylindrical electrode.
 17. Anapparatus according to claim 11, wherein the actuator is for translatingthe second generally cylindrical inner electrode synchronously with thefirst generally cylindrical inner electrode, such that the gap betweenthe first generally cylindrical inner electrode and the second generallycylindrical inner electrode is approximately constant duringtranslation.
 18. A method for controllably varying specificity of aFAIMS-based ion separation, comprising: providing a FAIMS analyzerregion having an ion inlet for introducing a flow of ions thereto andhaving an ion outlet for extracting a subset of the flow of ions that isselectively transmitted along an average ion flow path between the ioninlet and the ion outlet; introducing a first flow of ions into theFAIMS analyzer region via the ion inlet; selectively transmitting asubset of the first flow of ions along the average ion flow path throughthe FAIMS analyzer region; relatively translating the ion inlet relativeto the ion outlet so as to provide an average ion flow path of adifferent length through the FAIMS analyzer region; and, transmittingions of a second flow of ions along the average ion flow path of adifferent length.
 19. A method according to claim 18, wherein an ioncomposition of the first flow of ions is substantially the same as anion composition of the second flow of ions.
 20. A method according toclaim 19, wherein transmitting ions of the second flow of ions comprisesselectively transmitting a subset of the second flow of ions, an ioncomposition of the subset of the second flow of ions being differentthan an ion composition of the subset of the first flow of ions.
 21. Amethod according to claim 19, wherein transmitting ions of the secondflow of ions comprises transmitting a set of ions having an ioncomposition substantially the same as the ion composition of the secondflow of ions.
 22. A method according to claim 18, wherein the FAIMSanalyzer region is defined by a space between a first electrode surfaceand a second electrode surface, the first electrode surface disposed ina facing arrangement relative to the second electrode surface and spacedapart therefrom along a first direction, the first electrode surfacedefining the ion inlet and the second electrode surface defining the ionoutlet, and wherein changing the length of the average ion flow pathcomprises relatively translating the first electrode surface relative tothe second electrode surface along a second direction normal to thefirst direction.
 23. An apparatus for controllably varying specificityof a FAIMS-based ion separation, comprising: a FAIMS analyzer regiondefined between a first electrode surface and a second other electrodesurface, the FAIMS analyzer region in communication with an ionizationsource for providing a flow of ions including a known ion, and with anion outlet for extracting ions including the known ion from the FAIMSanalyzer region, the first and second electrode surfaces for having anasymmetric waveform voltage applied thereacross for defining an averageion flow path for the known ion traversing therebetween; and, anactuator for controllably moving the first electrode surface relative tothe second electrode surface for controllably varying the length of theaverage ion flow path.
 24. An apparatus for controllably varyingspecificity of a FAIMS-based ion separation, comprising: a FAIMSanalyzer region controllably switchable between a low specificity modeof operation and a high specificity mode of operation and defined by atleast a space between a plurality of spaced-apart electrode surfaces,the FAIMS analyzer region in communication with an ionization source forproviding a flow of ions including a known ion, and with an ion outletfor extracting ions including the known ion from the FAIMS analyzerregion, wherein switching between the low specificity mode of operationand the high specificity mode of operation is accomplished byrepositioning at least one electrode surface of the plurality ofspaced-apart electrode surfaces relative to another electrode surface ofthe plurality of spaced-apart electrode surfaces.